The complications of diabetes continue to be a major source of morbidity and mortality. The Epidemiology of Diabetes Complications Study has examined the prevalence and incidence of and risk factors contributing to diabetes complications for 14 years. This renewal proposes to continue examining these issues as they relate to population subgroups and specific complications. The study population is a well-defined cohort of type 1 diabetic patients identified from Children's Hospital of Pittsburgh Registry. All 658 examined subjects at baseline (1986-1988) were diagnosed between 1950-80. Subjects have been seen biennially since and are now in their 14th year of follow-up. During the proposed renewal period, we plan to conduct an annual general survey follow-up of the entire cohort (including the 658 examined at baseline who are still active and the 130 who provided only baseline questionnaires to further determine the presence of diabetes complications and associated risk factors. At 18 years a repeat exam will be done on those previously examined. Specifically we aim to: examine the role of Electron Beam Computed Tomography (EBT) determined coronary calcification (and of its rate of progression) and arterial to venous ratio on the prediction of coronary artery disease, determine risk factors for the progression of nephropathy (decline of renal function determined by standard clinical and serum cystatin-C measures), identify the predictors of clinically significant distal neuropathy by examination of the temporal relationship of risk factors, particularly inflammatory markers, to neuropathy presentation and progression), and to conduct further statistical, and temporal trend analyses of diabetes complications using the 18-20 year follow-up data set that will become available during this renewal period. Finally, we will collaborate with 4 other investigators, to increase our analytical power for EBT analyses, and permitting valuable comparisons, including use of the non-diabetic control subjects being examined in these studies. This study will continue to advance our knowledge of diabetes complications and lead to appropriate preventive strategies.